COGNITIVE TRAINING AND NEUROPLASTICITY IN MILD COGNITIVE IMPAIRMENT

轻度认知障碍（MCI）在老年人中很常见，是阿尔茨海默氏症的高危人群 疾病（AD）。生物标志物评估的进展改善了临床AD的早期诊断， MCI的药物试验通常失败。关于大脑可塑性的新发现导致了 认知训练作为提高认知能力的治疗方法的研究。计算机认知训练（CCT） 提供了一个令人兴奋的机会和一个新的策略，以改善认知表现的MCI。CCT涉及 针对特定能力/神经网络的计算机化认知练习，以潜在地提高认知能力 通过神经可塑性发挥作用。在一项双中心研究（NYSPI/哥伦比亚和杜克）中，我们将随机分配100名 MCI患者（广义上定义为包括如阿尔茨海默病中定义的eMCI和lMCI） 神经影像学倡议，ADNI）到CCT（一套练习）或主动控制条件（填字游戏）。 最初的12周将涉及强化CCT或主动控制条件，随后将进行定期 总共18个月的强化治疗我们有大量的试点数据，有力地支持这一计划 approach.我们将解决三个尚未在一口井中系统解决的关键问题- MCI的对照研究：CCT是否导致认知功能改善，CCT是否转移到 功能能力和日常生活的任务，以及CCT是否会导致大脑网络的长期变化，例如， 默认模式网络（DMN）使用静息功能磁共振成像？我们的目标是评估认知和功能的变化， 比较CCT与活性对照条件，并假设 在18个月的试验结束时，接受主动CCT的MCI患者将显示出更好的认知和功能结局。 我们还将研究一个无监督的基于网络的神经心理电池的敏感性和有效性 （脑功能测试，BPT）用于检测CCT效应及其与认知和 MCI中的功能性措施。我们还假设随机分配至CCT的MCI患者将显示出更大的 与对照条件相比，静息fMRI下DMN的变化，这些变化将是 与特定认知测试的改善有关。我们将比较过渡到临床 两组AD的诊断，并探讨改善的潜在调节因素，包括海马 以及内嗅皮质萎缩、嗅觉识别缺陷和载脂蛋白E ε 4等位基因状态。改善 老年人的认知，特别是那些有高风险转变为临床AD的老年人，是一个重要的公共卫生问题。 目标.如果研究目标得以实现，它将对改善生活质量和减少死亡率产生重大影响。 残疾和医疗保健成本在这个不断增长的人口。本研究与NIA AD 2015一致 峰会的建议和NIA的优先事项，以及向患者驱动的个性化医疗的运动。

Mild cognitive impairment (MCI) is common in older adults and represents a high-risk group for Alzheimer's disease (AD). Advances in biomarker assessment have improved the early diagnosis of clinical AD but medication trials in MCI have generally failed. New discoveries about brain plasticity in aging have led to the study of cognitive training as a treatment to improve cognitive abilities. Computerized Cognitive Training (CCT) provides an exciting opportunity and a new strategy to improve cognitive performance in MCI. CCT involves computerized cognitive exercises that target specific abilities/neural networks to potentially improve cognitive functioning through neuroplasticity. In a two-site study (NYSPI/Columbia and Duke) we will randomize 100 patients with MCI (broadly defined to include eMCI and lMCI as defined in the Alzheimer's Disease Neuroimaging Initiative, ADNI) to CCT (suite of exercises) or an active control condition (crossword puzzles). The initial 12 weeks will involve intensive CCT or active control conditions and this will be followed by regular booster sessions for a total of 18 months. We have extensive pilot data that strongly support this planned approach. We will address three key issues that have not been addressed systematically in a single well- controlled study in MCI: does CCT lead to improved cognitive functioning, do the effects of CCT transfer to functional ability and tasks of everyday life, and does CCT lead to long-term changes in brain networks, e.g., the default mode network (DMN) using resting fMRI? We aim to assess change in cognitive and functional status over 18 months in MCI patients comparing CCT versus active control condition, and hypothesize that MCI patients on active CCT will show better cognitive and functional outcomes by the end of the 18-month trial. We will also examine the sensitivity and validity of an unsupervised web-based neuropsychological battery (Brain Performance Test, BPT) for detecting CCT effects and its associations with change in cognitive and functional measures in MCI. We also hypothesize that patients with MCI randomized to CCT will show greater changes in the DMN with resting fMRI compared to the control condition and that these changes will be associated with improvement on specific cognitive tests. We will compare rates of transition to a clinical diagnosis of AD in the two groups, and explore potential moderators of improvement, including hippocampal and entorhinal cortex atrophy, olfactory identification deficits, and apolipoprotein E ε4 allele status. Improving cognition in older adults, especially those at high risk of transitioning to clinical AD, is an important public health goal. If the study goals are achieved it will have major implications for improving quality of life and reducing disability and healthcare costs in this growing demographic. This study is consistent with the NIA AD 2015 summit recommendations and NIA priorities, and the movement toward patient-driven personalized medicine.